Vinyl Chloride Toxicity

Vinyl chloride toxicity is poisoning from inhaling vinyl chloride monomer. Acute exposure causes narcosis. Chronic exposure causes a syndrome of Raynaud phenomenon, acro osteolysis, scleroderma like skin change and liver fibrosis, with a risk of liver cancer.

Exposure. Polyvinyl chloride manufacture and polymerisation reactors, particularly cleaning of autoclaves, and vinyl chloride production. Past exposure was heavy; levels are now strictly controlled in many regions.

Epidemiology. Cases follow years of heavy exposure. Highest risk is in reactor cleaners.

Chronic disease. Hepatic fibrosis with portal hypertension, splenomegaly and thrombocytopenia, and vascular and skeletal manifestations.

Cancer. Hepatic angiosarcoma is the signature tumour, with hepatocellular carcinoma, and possibly brain and lung tumours.

Pathophysiology.

Cytochrome P450 2E1 converts vinyl chloride to chloroethylene oxide and chloroacetaldehyde, reactive electrophiles that form DNA adducts (such as N2,3-ethenoguanine) and protein adducts.

Immune complex deposition and endothelial injury underlie Raynaud and scleroderma like change. Hepatotoxicity leads to perisinusoidal and portal fibrosis, and sinusoidal injury.

• Acute: dizziness, headache, nausea, drowsiness, confusion and loss of consciousness; skin cold injury from liquid.
• Chronic: Raynaud phenomenon, pain and swelling of the fingers, and shortening of distal phalanges.
• Skin thickening of the hands and forearms.
• Hepatosplenomegaly, abdominal pain, varices and thrombocytopenia.
• Neuropathy, fatigue, reduced libido and impotence.

Red flags.

• Abdominal distension, weight loss or new liver mass (angiosarcoma).
• Haematemesis or melaena (variceal bleeding).
• Digital ulceration or gangrene.

• Detailed exposure history with duration, reactor cleaning and respiratory protection.
• Full blood count (platelets), liver function, prothrombin time, albumin, hepatitis serology, and autoimmune screen including cryoglobulins and antinuclear antibodies.
• Abdominal ultrasound with Doppler for portal hypertension and spleen size; MRI or contrast CT for any lesion; transient elastography for fibrosis.
• Hand radiographs for acro osteolysis; nailfold capillaroscopy and cold challenge testing for Raynaud.
• Upper endoscopy for varices when portal hypertension is suspected.
• Liver biopsy when imaging and serology are inconclusive.
• Urinary thiodiglycolic acid is a non-specific marker of recent exposure.

Differential diagnosis. Primary Raynaud phenomenon, systemic sclerosis, vibration white finger, viral and alcoholic liver disease, non-alcoholic fatty liver disease, idiopathic non-cirrhotic portal hypertension, other causes of liver cancer, other occupational toxic hepatopathy.

• Remove from exposure; acute exposure needs fresh air, oxygen, and supportive care. No antidote exists. Avoid adrenaline. Treat cold injury from liquid contact as a freezing injury.
• Raynaud phenomenon: keep the hands warm, stop smoking, and avoid vasoconstrictors. Nifedipine modified release 30 mg orally once daily, increased after 2 weeks to 60 mg daily if needed. Usual maximum 60 mg daily. Monitor blood pressure, ankle oedema and headache. Reduce dose in hepatic impairment; no renal adjustment; avoid in pregnancy unless benefit outweighs risk.
• Portal hypertension: screening endoscopy; carvedilol 6.25 mg orally once daily for 3 days, then 12.5 mg once daily, long term. Maximum 12.5 mg daily for this use. Monitor blood pressure (keep systolic over 90 mmHg) and heart rate. Avoid in asthma, high degree heart block and bradycardia; caution in decompensated cirrhosis and renal impairment.
• Variceal bleeding: emergency admission with resuscitation, vasoactive drug and endoscopic band ligation by usual practice.
• Acro osteolysis: protect fingers, analgesia and hand therapy; no specific drug is available.
• Surveillance for hepatic angiosarcoma and hepatocellular carcinoma with ultrasound or MRI every 6 to 12 months for exposed workers with fibrosis; practice varies. Resection or oncology care for confirmed tumours.

Monitoring. Liver function, platelets and ultrasound every 6 to 12 months; endoscopy at diagnosis of portal hypertension and as directed by findings.

Referral and escalation. Hepatology and occupational physician at diagnosis; vascular and rheumatology review for digital ischaemia; oncology for any hepatic mass; notification and compensation where required.

Special groups. Pregnancy: avoid nifedipine unless needed and avoid carvedilol without specialist review. Hepatic impairment: reduce doses and avoid hepatotoxins.